Synthetic Concept Research Articles

Synthetic aperture probe and ultrasonic testing

Application of synthetic aperture probes to ultrasonic testing is discussed using as an illustration the dry-contact between two metal surfaces. Synthetic aperture concept uses the motion of the realistic probe over a target region to provide finer spatial resolution than conventional realistic transducer. Typically, the larger the aperture, the higher the image resolution is. We compared results, obtained applying synthetic aperture procedure to standard spherically focused probe with goal to synthesize the large aperture, and results, obtained using novel cylindrically focused transducer with real large aperture. Obtained experimental results confirmed efficiency of synthetic aperture concept in time domain and frequency domain.

An integrated engineering worldview of synthetic biology education through the lens of webinar based pedagogy.

Synthetic biology is an interdisciplinary field that brings together engineering and biology concepts alongside the arts and social sciences to develop solutions to pressing problems in our world. The education of students entering this field has relied on a diverse set of pedagogical methods to accomplish this goal. One non-profit group, iGEM-the International Genetically Engineered Machine competition, has been a driver of students' awareness of synthetic biology for the last 20 years giving many young researchers their first experience in the field of synthetic biology. Dissemination of synthetic biology concepts by iGEM has occurred through several programs including a webinar series started during the 2020 COVID pandemic. The iGEM webinar series successfully engaged students by taking inspiration from synthetic biology programs in Europe, North America, and Asia that had themselves evolved alongside iGEM. The webinar designers modeled the content after their experiences in iGEM as well as their academic courses, pedagogy, and mentoring experiences. This series has produced globally accessible pedagogy for both technical synthetic biology knowledge and the communication skills necessary to build and communicate synthetic biology projects. The hope is that this series functions as a lasting blueprint that can be used by future educators in synthetic biology and other disciplines to reduce barriers that students face when attempting to enter cutting edge fields.

Inhibition of PRMT5 moderately suppresses prostate cancer growth in vivo but enhances its response to immunotherapy

Protein arginine methylation is a common post-translational modification (PTM) catalyzed by nine protein arginine methyltransferases (PRMTs). As the major symmetric arginine methyltransferase that methylates both histone and non-histone substrates, PRMT5 plays key roles in a number of biological processes critical for development and tumorigenesis. PRMT5 overexpression has been reported in multiple cancer types including prostate cancer (PCa), but the exact biological and mechanistic understanding of PRMT5 in aggressive PCa remains ill-defined. Here, we show that PRMT5 is upregulated in PCa, correlates with worse patient survival, promotes corrupted RNA splicing, and functionally cooperates with an array of pro-tumorigenic pathways to enhance oncogenesis. PRMT5 inhibition via either genetic knockdown or pharmacological inhibition reduces stemness with paralleled differentiation and arrests cell cycle progression without causing appreciable apoptosis. Strikingly, the severity of antitumor effect of PRMT5 inhibition correlates with disease aggressiveness, with AR+ PCa being less affected. Molecular characterization pinpoints MYC, but not (or at least to a lesser degree) AR, as the main partner of PRMT5 to form a positive feedback loop to exacerbate malignancy in both AR+ and AR— PCa cells. Inspired by the surprising finding that PRMT5 negatively correlates with tumor immune infiltration and transcriptionally suppresses an immune-gene program, we further show that although PRMT5 inhibitor (PRMT5i) EPZ015666 or anti-PD-1 immunotherapy alone exhibits limited antitumor effects, combination of PRMT5i with anti-PD-1 displays superior efficacy in inhibiting castration-resistant PCa (CRPC) in vivo. Finally, to expand the potential use of PRMT5i through a synthetic lethality concept, we also perform a global CRISPR/Cas9 knockout screen to unravel that many clinical-grade drugs of known oncogenic pathways can be repurposed to target CRPC when used in combination with PRMT5i at low doses. Collectively, our findings establish a rationale to exploit PRMT5i in combination with immunotherapy or other targeted therapies to treat aggressive PCa.

Monge Surfaces. Generation, Discretisation and Application in Architecture

AbstractThis paper describes a revision of so-called Monge surfaces through using digital graphic tools, based on the synthetic conception exposed by Gaspard Monge in the 18th and 19th centuries, through their geometric relation with polar surface. As a starting point, we propose a graphical system that integrally solves the generation of these kind of surfaces, their rationalization and discretization, with the objective of their specific application in architecture. The geometric system described allows the generation of a type of surface in which the pair of curves -generatrix and directrix- give rise to the network of principal lines of curvature (LCP) of the final surface. In this way, we propose a process that follows a bottom-up generative system based on Monge surfaces, which offers wide possibilities of formal exploration, while imposing geometrical-constructive properties that are very useful in fabrication and assembly processes.

Orchestrated Octuple C−H Activation: A Bottom‐Up Topology Engineering Approach toward Stimuli‐Responsive Double‐Heptagon‐Embedded Wavy Polycyclic Heteroaromatics

AbstractCuriosity‐driven innovations on the design and synthesis of nonplanar polycyclic aromatic/heteroaromatic compounds with new molecular topologies unfold exciting opportunities for harnessing their intriguing supramolecular properties and thereby the development of novel functional organic materials. This work presents such an innovative synthetic concept of a bottom‐up molecular topology engineering through a unique orchestrated octuple C−H activation reaction, toward the rapid synthesis of a novel class of double heptagon‐incorporated nitrogen‐doped laterally‐fused polycyclic compounds with rarely reported wavy structural configuration. The profound impact of the molecular wavy structures of these compounds on their properties is manifested by weak and tunable solid‐state intermolecular interactions controlling the electronic properties of the materials, leading to reversibly switchable fluorochromism in the solid state and thin films with mechanical force and solvent vapors as external stimuli, thereby indicating their potential applicability in rewritable fluorescent optical recording media, security papers, mechanosensors, volatile organic compound (VOC) sensors etc.

Orchestrated Octuple C-H Activation: A Bottom-Up Topology Engineering Approach toward Stimuli-Responsive Double-Heptagon-Embedded Wavy Polycyclic Heteroaromatics.

Curiosity-driven innovations on the design and synthesis of nonplanar polycyclic aromatic/heteroaromatic compounds with new molecular topologies unfold exciting opportunities for harnessing their intriguing supramolecular properties and thereby the development of novel functional organic materials. This work presents such an innovative synthetic concept of a bottom-up molecular topology engineering through a unique orchestrated octuple C-H activation reaction, toward the rapid synthesis of a novel class of double heptagon-incorporated nitrogen-doped laterally-fused polycyclic compounds with rarely reported wavy structural configuration. The profound impact of the molecular wavy structures of these compounds on their properties is manifested by weak and tunable solid-state intermolecular interactions controlling the electronic properties of the materials, leading to reversibly switchable fluorochromism in the solid state and thin films with mechanical force and solvent vapors as external stimuli, thereby indicating their potential applicability in rewritable fluorescent optical recording media, security papers, mechanosensors, volatile organic compound (VOC) sensors etc.

Abstract B008: Utilizing pathway incompatibility for synthetic lethality: A therapeutic strategy for B-cell lymphoma

Abstract Previous pan-cancer analyses revealed co-occurring mutations exploitable for combination therapies and mutually exclusive mutations assumed to reflect functional redundancy (Mina M et al. 2017; Sanchez-Vega F et al. 2018). However, we recently highlighted an alternative scenario when mutual exclusivity reflects the incapability of two pathways to function together, a phenomenon we term “pathway incompatibility” (Chan LN et al. 2020). We found that STAT5-and ERK-activating genetic lesions were not only mutually exclusive in B-ALL cases, but also reciprocally inhibited each other at the signal transduction level, inducing cell death instead of promoting leukemogenesis. Notably, we demonstrated, for the first time, that pharmacological activation of STAT5 in ERK-driven B-ALL cells and ERK in STAT5-driven B-ALL cells represents a tractable synthetic lethality (Chan LN et al. 2020). We now take the important next step of identifying potential candidates for synthetic lethal genetic interactions resulting from pathway incompatibility in B-cell malignancies more broadly. Diffuse large B-cell lymphoma (DLBCL) is a rapidly growing blood cancer affecting older adults and constituting about 25% of all lymphoma cases in the US. Around 40% of patients develop relapsed or refractory DLBCL (Pfreundschuh M et al. 2006; Ngu H et al. 2022). Thus, there is an unmet need to develop new therapeutic strategies to improve clinical outcomes. Studying 1684 DLBCL cases from published datasets, we found that about 30% of DLBCL cases carry loss-of-function (LOF) CBP or gain-of-function (GOF) MYD88 genetic lesions. CBP encodes a histone acetyltransferase and, together with p300, functions as a transcriptional coactivator and tumor suppressor. Conversely, GOF MYD88 mutations drive lymphomagenesis by regulating kinases and transcription factors. Our analysis revealed that LOF CBP and GOF MYD88 genetic lesions co-occurred less frequently than expected by chance (odds ratio: 0.57, P=0.0), indicating their mutual exclusivity. Experiments with human DLBCL cell lines expressing wild-type MYD88 and CBP showed that CBP/p300 inhibitors did not impact cell viability. However, cells expressing a GOF MYD88 mutant or stimulated with a toll-like receptor (TLR) agonist to activate MYD88 became sensitized to CBP/p300 inhibitors, resulting in cell death. This suggests that LOF CBP and GOF MYD88 are incompatible for cell survival, with their co-occurrence resulting in synthetic lethality. We then tested a synthetic lethality-based therapeutic concept based on CBP-MYD88 incompatibility in DLBCL. We found that MYD88-mutated DLBCL cell lines were more sensitive to pharmacological inhibition of CBP/p300, while CBP-deficient DLBCL cell lines showed increased sensitivity to TLR agonist treatment. In summary, we identified mutual exclusivity between LOF CBP and GOF MYD88 lesions in DLBCL, where their co-occurrence induces cell death. Moreover, we demonstrated the therapeutic potential of synthetic lethality resulting from co-introduction of LOF CBP and GOF MYD88 in DLBCL. Citation Format: Mia Knupke, Lai Chan. Utilizing pathway incompatibility for synthetic lethality: A therapeutic strategy for B-cell lymphoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B008.

Ionic hyper-cross-linked porous polymer networks with achiral and chiral pyridinium-type segments

A new type of ionic porous polymer networks (PPNs) is reported containing (i) N-alkyl pyridinium bromide ionic groups and (ii) a hyper-cross-linked scaffold based on polyacetylene (polyene) chains the rigidity of which contributes to the permanent porosity the PPNs. The ionic PPNs were prepared by a combination of chain-growth polymerization of acetylenic monomers and quaternization reactions of pyridine and alkyl bromide moieties. The wide variability of this synthetic concept enabled the preparation of covalently diverse PPNs with ionic groups located either in the pendant groups or in the knots of the networks, as well as the preparation of PPNs with chiral ionic groups. The content of ionic groups in PPNs ranged from 1.5 to 4.2 mmol/g, and the BET area was from 67 to 744 m2/g. The mode of quaternization used (prepolymerization or postpolymerization) controlled the contribution of micropores and mesopores to the porosity of the ionic PPNs. The polyacetylene ionic PPNs were active as heterogeneous organocatalysts (applied without a cocatalyst) for the cycloaddition of CO2 to styrene oxide yielding styrene carbonate as the only product (up to 96 %). PPNs with chiral ionic groups showed potential for enantioselective catalysis of this reaction. The catalytic activity was controlled by the accessibility of pyridinium active centres for the substrate molecules. Ionic PPNs prepared were also efficient in reversible water vapour capturing and releasing (capacity up to 361 mg/g at 298 K and RH = 90 %). Both surface adsorption and capillary condensation of H2O contributed to the water vapour capture on reported PPNs.

Cyclic Deracemization of rac‐Sulfoxides via Alternating Biocatalytic Reduction and Light‐Dependent Oxidation Employing Eosin Y as Photocatalyst

AbstractThe synergistic combination of biocatalysis and photocatalysis is emerging as powerful tool for the development of sustainable and atom‐efficient synthetic concepts facilitating an enormous portfolio of possible reactions which even goes beyond the capabilities found in nature. Here, a cyclic deracemization process is presented tailored for the synthesis of optically pure sulfoxides which are versatile structural motifs in asymmetric synthesis as well as in bioactive compounds. Enantioselective enzyme‐catalyzed reduction of rac‐sulfoxides was combined with a stereo‐unselective photocatalytic oxidation of the corresponding sulfide intermediate. The utilization of the readily accessible and rather inexpensive photocatalyst Eosin Y increases the usability of this synthetic method. To overcome the incompatibility between the photocatalyst Eosin Y and the biocatalytic step, the cyclic deracemization process was performed in a step‐wise fashion via alternated reduction in the darkness and oxidation under illumination. This modular system allowed precise adjustments of reaction parameters yielding the desired sulfoxide targets with up to >99 % ee. Evaluation of the substrate scope including a range of structurally diverse molecules demonstrated its broad applicability.

Georq Vilhelm Fridrix Hegel fəlsəfəsində analitik və sintetikin fərqi

The main goal of the article is to briefly review the difference between analytical and synthetic in Hegel's philosophy, as well as to determine whether this philosopher was a follower of Kant's philosophy or not. First, in the "Introduction" section, the difference between analytical and synthetic in Kant's philosophy is shown; moreover, Kant's influence on Hegel and, generally, on the period in question and the conclusions of both scientists on this issue are analyzed. In the article, the main features of Hegel's and Kant's worldviews and some conclusions related to the pair of concepts in Hegel's philosophy, i.e., analytical and synthetic concepts, are examined. In the conclusion of the article, Hegel's main philosophical views are identified, and the possibility of resolving the difference between analytical and synthetic through dialectical judgment is put forward.

BRCA1/2 alterations and reversion mutations in the area of PARP inhibitors in high grade ovarian cancer: state of the art and forthcoming challenges.

BRCA1/2 genes are part of homologous recombination (HR) DNA repair pathways in charge of error-free double-strand break (DSB) repair. Loss-of-function mutations of BRCA1/2 genes have been associated for a long time with breast and ovarian cancer hereditary syndrome. Recently, polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) have revolutionized the therapeutic landscape of BRCA1/2-mutated tumors, especially of BRCA1/2 high-grade serous ovarian cancer (HGSC), taking advantage of HR deficiency through the synthetic lethality concept. However, PARPi efficiency differs among patients, and most of them will develop resistance, particularly in the relapse setting. In the current proposal, we aim to review primary and secondary resistance to PARPi in HGSC owing to BRCA1/2 alterations. Of note, as several mechanisms of primary or secondary resistance to PARPi have been described, BRCA1/2 reversion mutations that restore HR pathways are by far the most reported. First, the type and location of the BRCA1/2 primary mutation have been associated with PARPi and platinum-salt sensitivity and impact the probability of the occurrence and the type of secondary reversion mutation. Furthermore, the presence of multiple reversion mutations and the variation of allelic frequency under treatment underline the role of intratumor heterogeneity (ITH) in treatment resistance. Of note, circulating tumor DNA might help us to detect and characterize reversion mutations and ITH to finally refine the treatment strategy. Importantly, forthcoming therapeutic strategies, including combination with antiangiogenics or with targeted therapies, may help us delay and overcome PARPi resistance secondary to BRCA1/2 reversion mutations. Also, progression despite PARPi therapy does not preclude PARPi rechallenge in selected patients.

An Analysis of the Development of Preschoolers’ Natural Science Concepts from the Perspective of Framework Theory

The aim of the study was to explore children’s learning of natural science, and the authors chose a literature review as the means to achieve this aim. As the research into children’s emerging science is fragmented into many different theoretical perspectives and many kinds of studies are included, research results deriving from the field can be difficult to summarize. To resolve this issue, Vosniadou’s framework theory was used as the tool for data analysis. Results show emergence as a dynamic interaction between intuitive and counter-intuitive concepts leading to synthetic and scientific models in combination with developing epistemological and ontological skills. The accumulation of synthetic concepts seems to be the most common result of early formal educational input. Both intuitive and synthetic models are predecessors for scientific concepts and models, and these models as such are very important for emerging science. The conclusions suggest that diverse science experiences should bring about more synthetic models. This subsequently creates a wider basis for further development. Another important factor of emergence is the development of children’s epistemic skills and ontological shifts. Research results suggest that it is important for teachers to support children’s epistemic and ontological skills. Enhancing children’s understanding about causality and ontology is an important step towards developing formal concepts of science.

Electronic and optical properties of core-shell InAlN nanorods: a comparative study via LDA, LDA-1/2, mBJ, HSE06, G0W0 and BSE methods.

Currently, self-induced InAlN core-shell nanorods enjoy an advanced stage of accumulation of experimental data from their growth and characterization as well as a comprehensive understanding of their formation mechanism by the ab initio modeling based on Synthetic Growth Concept. However, their electronic and optical properties, on which most of their foreseen applications are expected to depend, have not been investigated comprehensively. GW and the Bethe-Salpeter equation (BSE) are regarded as the state-of-the-art ab initio methodologies to study these properties. However, one of the major drawbacks of these methods is the computational cost, much higher than density-functional theory (DFT). Therefore, in many applications, it is highly desirable to answer the question of how well approaches based on DFT, such as e.g. the local density approximation (LDA), LDA-1/2, the modified Becke-Johnson (mBJ) and the Heyd-Scuseria-Ernzerhof (HSE06) functionals, can be employed to calculate electronic and optical properties with reasonable accuracy. In the present paper, we address this question, investigating how effective the DFT-based methodologies LDA, LDA-1/2, mBJ and HSE06 can be used as approximate tools in studies of the electronic and optical properties of scaled down models of core-shell InAlN nanorods, thus, avoiding GW and BSE calculations.

Impact of BSA and Au3+ concentration on the formation and fluorescence properties of Au nanoclusters.

Bovine serum albumin-stabilized Au nanoclusters (BSA-Au NCs) have emerged as promising contenders for imaging agents and highly sensitive fluorescence sensors due to their biocompatibility and strong photoluminescence. Optimizing the synthesis conditions of BSA-Au NCs is crucial for enhancing fluorescence imaging and other nanocluster applications. In this study, for the first time, we systematically investigated the effects of BSA concentration and Au3+ on both particle size and optical characteristics of BSA-Au NCs. When the two components achieved a suitable concentration ratio, it was beneficial to form BSA-Au NCs with a high quantum yield (QY = 74.30%) and good fluorescence stability. In contrast, an inappropriate concentration ratio would lead to the formation of gold nanoparticles (Au NPs), and their internal filtration effect (IFE) would attenuate the fluorescence emission of BSA-Au NCs. The BSA-Au NCs were then employed as efficient fluorescence sensors for detecting Hg2+. Furthermore, the growth mechanism of BSA-Au NCs was elucidated by monitoring fluorescence changes during different incubation times. The BSA-Au NCs with a high quantum yield introduce a novel synthetic concept for sensitive fluorescent probes and expanding versatile applications of BSA-Au NCs in catalysis, chemical sensing and biomedicine.

Synthetic concept of working with dreams: approbation in the field of psychological psychotherapy and personality development

This paper presents the results of a scientific study aimed at determining the effectiveness of the synthetic concept of dreams when applied in the field of psychological psychotherapy (psychocorrection) and (or) in the field of personality development. Accordingly, the mental reality of the subjects is presented as an object of research, and as its subject of research – "transformation of the states and (or) personality characteristics of the participants in the experiment in the context of the use of a synthetic algorithm for working with dreams." The research was conducted in the form of an experiment, the participants of which, in interaction with the experimenter, who performed the function of interpreter and "guide", comprehended their dreams and carried out direct work with them. The main conclusions drawn on the basis of the results of the study were the confirmation of the effectiveness of the presented synthetic concept of dreams and, therefore, the idea of dreaming as a natural psychotherapeutic (psychocorrective) mechanism, as well as the material with which work contributes to the development of personality. Taking into account the high scientific interest and practical significance of studying the integral structure of a person's mental reality in the context of improving his psychological well-being in a stressful environment and, at the same time, the known complexity of the study of such a phenomenon as dreams, the work can claim the status of one of the steps to scientific discovery.

СТАНОВЛЕНИЕ ЭКОЛОГИЧЕСКОГО ИДЕАЛА В КОНТЕКСТЕ КОНЦЕПЦИИ ИДЕАЛЬНОГО Д. В. ПИВОВАРОВА

The author addresses the urgent problem of the formation and development of a new ecological culture as a strategically important task in the conditions of the ecological crisis. Developing the heuristic potential of the synthetic concept of culture and D. V. Pivovarov’s concept of the ideal, the author analyzes the possibility of understanding the essence of ecological culture based on this concept, the possibility of constructing the ecological culture of the future society based on the concept of the ideal. The key importance of the ideal in the formation of culture is substantiated. The article discusses three models of idealization in the ecological context and the manifestations of these ways of idealization in modern reality. The author analyzes the birth of a new ecological ideal in the format of a specific subjective image of the objective world, embodied in numerous texts of ecophilosophists, which, according to the author, have a limited impact on the broad masses of the population. Тhe author sees the reasons for this in the scientific style of texts and the lack of attractiveness for a modern person of the world order proposed by ecophilosophists. The possibility of the emergence of ecological religion on the principles of metaconfessionality, ecocentrism and biocentrism is interpreted. Modern ecological practices are considered as the second way of idealization, which involves the transformation of activities based on the criterion of long-term, long-term and multidimensional benefits based on the universal value of nature and the remoteness of the consequences of environmental management. To effectively use this path of idealization, support from the state, the media, elites, etc. is needed. The transformation of images-ideals of an ecological nature, embodied, for example, in the change of the aesthetic ideal, is discussed. The article interprets ecotopia as an integral mechanism of idealization, reflecting all the listed models of idealization. As a result of the research, the problems of the correlation of ecological values and ideals with the values of individualism and collectivism are revealed, the need for a new understanding of the idea of the «common good», the search for the ecological meaning of the concept of «quality of life», the study of possible forms of the sacralization of nature in modern conditions is revealed. The results of the research can be used in the implementation of environmental policy to create conditions for the sustainable development of society, in pedagogical design of ways to form environmental values, in ecophilosophical research of the search for strategies for survival and sustainable development.

SOUL IN ABRAHAM POZOV’S ANTHROPOLOGY: THE SYNTHESIS OF TRADITIONS OF RELIGIOUS PHILOSOPHY AND SCIENTIFIC ACHIEVEMENTS OF THE 20th CENTURY

New information about man, obtained as a result of the development of science, promoted the revision of a number of issues in the relationship between God and man. To substantiate theological formulas, many religious philosophers resorted to the synthesis of different branches of knowledge. An important part of the new search was the definition of the essence and nature of soul. An example of this dynamics is the synthetic concept of A. Pozov, who was a representative of the religious philosophy of the Russian diaspora of the 20th century. A. Pozov’s theory demonstrates how well-established theological patterns transformed under the influence of scientific progress. At the same time, there are conceptual traditional foundations of religious and philosophical thought in his works. Thus, the synthetic concept of the soul in A. Pozov’s anthropology can be regarded as a result of the fusion of traditional concepts of religious and philosophical thought and the influence of scientific discoveries of the 20th century. Among other things, A. Pozov’s works trace the prerequisites for the formation of Christian psychology

Three Interpretations of Habermas’s Theory of Truth

These reflections are devoted to a critical comparison of three distinct interpretations of Habermas’s theory of truth. The first, which is presented as the more adequate interpretation, takes Habermas’s theory as having a three-moment structure, whereas the two remaining interpretations are both based on his two-moment conception of “Janus-faced truth”. Whereas Steven Levine stresses the nonepistemic lifeworld pole of the two-sided concept and Alex Seemann the opposite epistemic discursive pole, the three-moment interpretation counters with a synthetic conception which emphasises the role of the context-transcendent universalistic concept of truth. This overarching interpretation is inspired by a cognitive perspective concerned with the full circle of the sociocultural embodiment and realisation of reason.

Aroyl-S,N-Ketene Acetals: Luminous Renaissance of a Class of Heterocyclic Compounds.

Aroyl-S,N-ketene acetals represent a peculiar class of heterocyclic merocyanines, compounds bearing pronounced and rather short dipoles with great push-pull characteristics that define their rich properties. They are accessible via a wide array of synthetic concepts and procedures, ranging from addition-elimination and condensation procedures up to rearrangement and metal-mediated reactions. With our work from 2020, aroyl-S,N-ketene acetals have been identified as powerful and promising dyes with pronounced and vastly tunable solid-state emission and aggregation-induced emission properties. One characteristic trademark of this class of dye molecules is the level of control that could be exerted and which was thoroughly explored. Based on these results, the field was opened to extend the system to bi- and multichromophoric systems by the full toolkit of synthetic organic chemistry thus giving access to even more exciting properties and manifolded substance libraries capitalizing on the AIE properties. This review aims at outlining the reaction-based principles that allow for a swift and facile access to aroyl-S,N-ketene acetals, their methodological and structural evolution and the plethora of fluorescence and aggregation properties.

Ligand-Directed Chemistry on Glycoside Hydrolases - A Proof of Concept Study.

Selective covalent labelling of enzymes using small molecule probes has advanced the scopes of protein profiling. The covalent bond formation to a specific target is the key step of activity-based protein profiling (ABPP), a method which has become an indispensable tool for measuring enzyme activity in complex matrices. With respect to carbohydrate processing enzymes, strategies for ABPP so far involve labelling the active site of the enzyme, which results in permanent loss of activity. Here, we report in a proof of concept study the use of ligand-directed chemistry (LDC) for labelling glycoside hydrolases near - but not in - the active site. During the labelling process, the competitive inhibitor is cleaved from the probe, departs the active site and the enzyme maintains its catalytic activity. To this end, we designed a building block synthetic concept for small molecule probes containing iminosugar-based reversible inhibitors for labelling of two model β-glucosidases. The results indicate that the LDC approach can be adaptable for covalent proximity labelling of glycoside hydrolases.